Contact PD/PI: Bertisch, Suzanne Michele More than 10% of Americans suffer from migraine, a poorly understood chronic neurological syndrome, characterized by unpredictable, recurrent attacks marked by intense pain, altered cognitive functioning, and physiologic disturbances. Migraine ranks among the most disabling medical conditions, and costs $12 billion/year in lost employee time in the United States. Despite the high burden of migraine and the availability of targeted pharmacotherapy (i.e., triptans), effective treatment and prevention remains elusive for many patients. Disrupted sleep, including ?too short sleep,? is identified by >50% of migraine sufferers as a trigger of migraine, and clinical practice dictates sleep hygiene to migraineurs. Yet, few studies have examined the precise temporal relationships of specific sleep attributes that may provoke migraine, leaving a gap in our knowledge as to how nightly patterns of sleep, including short sleep duration and disturbed sleep, relate to next-day risk of migraine. Congruently, there are few data exploring the reciprocal pathway whereby migraine impacts sleep. We propose a novel cohort study to quantify the bidirectional, temporal relationship between a single night of short sleep duration and migraine onset. We will also explore the independent, temporal association between fragmented sleep (low sleep efficiency) and migraine. Lastly, we will explore if shifts in sleep midpoint and short periods of cumulative sleep loss (2 nights of short sleep) predict migraine onset. Addressing this knowledge gap has critical implications for the etiology, prevention and treatment of migraine. We prospectively collect daily objective (via actigraphy) for six weeks in 100 patients with migraine. Using a state-of-the-art epidemiologic approach?the self-controlled case series design, we will achieve two specific aims: (1) to quantify the independent contribution of sleep duration as a temporal precedent of migraine; (2) to identify the temporality and impact of other objective measures of disturbed sleep, including sleep fragmentation and shifts in sleep midpoint, as triggers of migraine. The proposed study will definitively establish the temporal relationship between short sleep duration and risk of migraine attacks. Refining our understanding of the causal role of sleep duration and sleep disruption in migraine pathogenesis would justify further investigations of novel, targeted interventions that modify specific aspects of sleep for persons with migraine. Our work will also generate insights for future research disentangling the neurobiologic processes linking sleep with migraine. We anticipate this proposed work would contribute substantively to our understanding of the bidirectional relationship between sleep and migraine and support innovative and aggressive management of sleep disruption in patients with migraine, thereby mitigating the enormous burden of this chronic neurovascular disease. Project Summary/Abstract Page 6